C-type lectin receptors Dectin-3 and Dectin-2 form a heterodimeric pattern-recognition receptor for host defense against fungal infection.

Abstract

C-type lectin receptors (CLRs) play critical roles as pattern-recognition receptors (PRRs) for sensing Candida albicans infection, which can be life-threatening for immunocompromised individuals. Here we have shown that Dectin-3 (also called CLECSF8, MCL, or Clec4d), a previously uncharacterized CLR, recognized α-mannans on the surfaces of C. albicans hyphae and induced NF-κB activation. Mice with either blockade or genetically deleted Dectin-3 were highly susceptible to C. albicans infection. Dectin-3 constantly formed heterodimers with Dectin-2, a well-characterized CLR, for recognizing C. albicans hyphae. Compared to their respective homodimers, Dectin-3 and Dectin-2 heterodimers bound α-mannans more effectively, leading to potent inflammatory responses against fungal infections. Together, our study demonstrates that Dectin-3 forms a heterodimeric PRR with Dectin-2 for sensing fungal infection and suggests that different CLRs may form different hetero- and homodimers, which provide different sensitivity and diversity for host cells to detect various microbial infections.

• Authors: Le-Le Zhu, Xue-Qiang Zhao, Changying Jiang, Yun You, Xiao-Ping Chen, Yuan-Ying Jiang, Xin-Ming Jia, Xin Lin
• Journal: Immunity (Immunity) Vol. 39 Issue 2 Pg. 324-34 (Aug 22 2013) ISSN: 1097-4180 [Electronic] United States
• PMID: 23911656 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Clecsf8 protein, mouse
• Lectins, C-Type
• Mannans
• Membrane Proteins
• NF-kappa B
• Receptors, Pattern Recognition
• dectin-2, mouse

Topics

• Animals
• Candida albicans (immunology)
• Candidiasis (immunology)
• Enzyme Activation
• Female
• Humans
• Hyphae (immunology, metabolism)
• Lectins, C-Type (deficiency, genetics, metabolism)
• Mannans (metabolism)
• Membrane Proteins (deficiency, genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• NF-kappa B (metabolism)
• Receptors, Pattern Recognition (immunology)
• Signal Transduction